Molecular Virology of Hepatitis B Virus and Targets for Antiviral Intervention

The members of the viral family Hepadnaviridae comprise one of the smallest enveloped DNA viruses and cause acute and chronic infections in mammals and birds, leading to large virus and antigen loads in the blood. They have a restricted host range and depend on differentiated hepatocytes for replication. Hepatitis B virus (HBV) is the prototype of the Hepadnaviridae. HBV can persist in infected hepatocytes and has evolved elaborate strategies to evade the immune system. HBV replicates like HIV (family of Retroviridae) via reverse transcription. Drugs licensed for inhibition of HIV reverse transcriptase lower the viral load of chronic HBV patients, but they do not cure the infection. HBV genomes are archived in the nucleus of hepatocytes as episomal DNA before reverse transcription. In contrast, the RNA genome of HIV first needs reverse transcription before proviral integration within the host genome. Wild-type HBV remains relatively stable in chronic HBV patients during the immunotolerant state, but is able to evolve mutants rapidly upon selective pressure due to therapy or immune reactions. Current therapies for chronic hepatitis B are far from optimal. To extend therapeutic options, further studies on HBV and its interaction with the host are urgently needed.